title: Analysis of CD97 expression and manipulation: antibody treatment but not gene targeting curtails granulocyte migration.
abstract: The heptahelical receptor CD97 is a defining member of the EGF-TM7 family of adhesion class receptors. In both humans and mice, CD97 isoforms are expressed with variable numbers of tandemly arranged N-terminal epidermal growth factor-like domains that facilitate interactions with distinct cellular ligands. Results from treatment of mice with mAbs in various disease models have suggested a role for CD97 in leukocyte trafficking. Here, we aimed to thoroughly characterize the expression profile of CD97, and delineate its biological function. To this end, we applied a novel polyclonal Ab, which is the first antiserum suitable for immunohistochemistry, and combined this analysis with the study of Cd97-lacZ knock-in mice. We show that similar to the situation in humans, hematopoietic, epithelial, endothelial, muscle, and fat cells expressed CD97. Despite this broad expression pattern, the Cd97(-/-) mouse that we created had no overt phenotype, except for a mild granulocytosis. Furthermore, granulocyte accumulation at sites of inflammation was normal in the absence of CD97. Interestingly, application of CD97 mAbs blocked granulocyte trafficking after thioglycollate-induced peritonitis in wild-type but not in knock-out mice. Hence, we conclude that CD97 mAbs actively induce an inhibitory effect that disturbs normal granulocyte trafficking, which is not perturbed by the absence of the molecule.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Henrike
authors.initials: H
authors.lastname: Veninga
authors.forename: Susann
authors.initials: S
authors.lastname: Becker
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoek
authors.forename: Manja
authors.initials: M
authors.lastname: Wobus
authors.forename: Elke
authors.initials: E
authors.lastname: Wandel
authors.forename: Jos
authors.initials: J
authors.lastname: van der Kaa
authors.forename: Martin
authors.initials: M
authors.lastname: van der Valk
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Hannelore
authors.initials: H
authors.lastname: Haase
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Owens
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aust
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000502:physiology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D018390:Gene Targeting / Q000379:methods; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C490633:Adgre5 protein, mouse; D000906:Antibodies; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled